SCID is a heterogenous group of disorders in children characterized by the absence of B-cell and T-cell immunity. Several forms of SCID in both humans and mice have been shown to result from mutations in cytoplasmic signaling kinases required to transduce T-cell antigen receptor events to intracellular biochemical pathways. The objective of this proposal is to gain insight into the roles of PTKs in T-cell signaling and thymic ontogeny by defining immunological conditions in humans in which activities of these signaling proteins are defective.